This conference will be the third in a regularly scheduled series of FASEB Summer Research Conferences devoted to molecular and cellular gerontology. Each conference is intended to focus on a different aspect of this broad topic, as dictated by recent research progress and orientation of other major gerontology conferences in the preceding and following year. In the current cycle, this special emphasis will be on DNA damage and repair as it relates to senescence and longevity and on the human disorders of premature aging that are also natural human mutants. In these areas there have been tremendous developments and the fields have moved from a descriptive stage to one of molecular and biochemical experimentation. In the conference we will have presentations from experts in DNA damage and repair (Drs. Kunkel, Friedberg, Bohr, Kraeemer and others). We will hear about the molecular and biochemical studies in Werners syndrome, Cockayne syndrome and Bloom syndrome (Drs. Oshima, Goto, Campisi, Bohr and others), we will have talks about cellular senescence and pathways involved (Drs. Campisi, Wang, and others), and we will learn about developments in the understanding of signal transduction pathways and their changes with aging (Drs. Karin, Christofalo and others). We will also have a session dealing with the most recent findings in genetics of aging in invertebrate model systems (Drs. Jazwinski, Johnson and Curtsinger). Funds are requested to defray expenses of invited speakers and of junior investigators and trainees who might otherwise not be able to attend the meeting, particularly those who would present their work in the open poster session. It is anticipated that participants will exchange recent data in the topic areas, as well as share diverse perspectives on molecular and cellular aging reflecting the disparate background of the participants. The conference is also specifically intended to recruit to the field of aging basic researchers whose work is highly relevant to molecular gerontology but not presently identified by them in this way. The exchange between investigators interested primarily in DNA damage and repair with those primarily interested in premature aging disorders should lead to important new insights and strategic approaches to major questions in gerontology today.